METHOD FOR PREPARING ANTINEOPLASTIC DRUG AGAINST BONE METASTASES IN FORM OF CONJUGATE OF PROTEIN-CYTOKINE AND AMINOBISPHOSPHONATE Russian patent published in 2017 - IPC A61K38/19 A61P35/04 

FIELD: pharmacology.

SUBSTANCE: conjugation reaction of aminobisphosphonate and the antineoplastic component using a cross-linker is carried out. Then the conjugation product is separated from the unbounded components of the reaction mixture. The human TNF-alpha protein is used as the antineoplastic component, alendronic acid is used as aminobisphosphonate, glutaraldehyde, or water-soluble N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide, or sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate(Sulfo-SCMM) is used as the cross-linker. Prior to conducting the conjugation reaction, alendronic acid or the TNF-alpha protein is pre-adsorbed on an insoluble hydroxylapatite carrier. The component adsorbed on the carrier is activated with the cross-linker, followed by washing of the mentioned agent. After the conjugate is formed on the carrier, the unbounded TNF-alpha protein is eluted first, and then the resulting conjugate of alendronic acid with the TNF-alpha protein is eluted. The resulting conjugate of the TNF-alpha protein with alendronic acid have a stoichiometric ratio of 1:1.

EFFECT: invention allows to synthesise a conjugate of a human TNF-alpha protein with alendronic acid with controlled stoichiometry, which preserves the antineoplastic activity of TNF-alpha and is directed against metastatic tumour of bone tissue.

4 cl, 11 dwg, 10 ex, 1 tbl